Mono- and bis-nitrosylated alkyl polyols for therapeutic use

Abstract

The present invention relates to the use of mono- and bis nitrosylated propanediols, and compositions and formulations comprising the same, in methods for the treatment of a microbial infection.

1 . A compound of formula (I): 
       
         
           
           
               
               
           
         
         wherein R 1 , R 2  and R 3  each independently represent H or —NO, 
         wherein n is 0 or 1; 
         wherein when n is 0, R 1  is H; and 
         wherein when n is 1, R 2  is H, 
         provided that at least one of R 1  R 2  and R 3  represents —NO, 
         for use in the treatment of a microbial infection. 
       
     
     
         2 . A method of treatment of a microbial infection in a subject, which method comprises administering a compound of formula (I): 
       
         
           
           
               
               
           
         
         wherein R 1 , R 2  and R 3  each independently represent H or —NO, 
         wherein n is 0 or 1; 
         wherein when n is 0, R 1  is H; and 
         wherein when n is 1, R 2  is H, 
         provided that at least one of R 1  R 2  and R 3  represents —NO, 
         to a subject in need of such treatment. 
       
     
     
         3 . The use of a compound of formula (I): 
       
         
           
           
               
               
           
         
         wherein R 1 , R 2  and R 3  each independently represent H or —NO, 
         wherein n is 0 or 1; 
         wherein when n is 0, R 1  is H; and 
         wherein when n is 1, R 2  is H, 
         provided that at least one of R 1  R 2  and R 3  represents —NO, 
         for the manufacture of a medicament for a method of treatment of a microbial infection. 
       
     
     
         4 . A compound for use as claimed in  claim 1 , a method of treatment as claimed in  claim 2 , or a use as claimed in  claim 3 , wherein the microbial infection is a parasitic, bacterial, fungal or viral infection. 
     
     
         5 . A compound for use, a method, or a use as claimed in  claim 4 , wherein the bacteria is selected from the group of gram-positive bacteria. 
     
     
         6 . A compound for use, a method, or a use as claimed in  claim 5 , wherein the bacteria is selected from the phylum Firmicutes, preferably wherein the bacteria is selected from the class Bacilli, preferably wherein the bacteria is selected from the order Bacillales, preferably wherein the bacteria is selected from the family Bacillaceae and/or Staphylococcaceae, preferably wherein the bacteria is selected from the genus  Bacillus  and/or  Staphylococcus , preferably wherein the bacteria is  Bacillus spizizenii  and/or  Staphylococcus aureus.    
     
     
         7 . A compound for use, a method, or a use as claimed in  claim 4 , wherein the bacteria is selected from the group of gram-negative bacteria. 
     
     
         8 . A compound for use, a method, or a use as claimed in  claim 7 , wherein the bacteria is selected from the phylum Proteobacteria, preferably wherein the bacteria is selected from the class Gammaproteobacteria, preferably wherein the bacteria is selected from the order Pseudomonadales, preferably wherein the bacteria is selected from the family Pseudomonadaceae, preferably wherein the bacteria is selected from the genus  Pseudomonas , preferably wherein the bacteria is  Pseudomonas aeruginosa.    
     
     
         9 . A compound for use, a method, or a use as claimed in  claim 4 , wherein the fungus is selected from the division Ascomycota. 
     
     
         10 . A compound for use, a method, or a use as claimed in  claim 9  wherein the fungus is selected from the class Saccharomycetes, or wherein the fungus is selected from the order Saccharomycetales, or wherein the fungus is selected from the family Saccharomycetaceae, or wherein the fungus is selected from the genus  Candida , or wherein the fungus is  Candida albicans.    
     
     
         11 . A compound for use, a method, or a use as claimed in  claim 9  wherein the fungus is selected from the class Eurotiomycetes, or wherein the fungus is selected from the order Eurotiales, or wherein the fungus is selected from the family Trichocomaceae, or wherein the fungus is selected from the genus  Aspergillus , or wherein the fungus is  Aspergillus brasiliensis.    
     
     
         12 . A compound for use, a method, or a use as claimed in  claim 4 , wherein the virus is selected from the realm Riboviria. 
     
     
         13 . A compound for use, a method, or a use as claimed in  claim 12  wherein the virus is selected from the phylum Incertae Sedis, or wherein the virus is selected from the order Nidovirales, or wherein the virus is selected from the family Coronaviridae, or wherein the virus is selected from the genus Betacoronavirus, or wherein the virus is selected from the subgenus Sarbecovirus, or wherein the virus is a SARS-CoV-2 virus. 
     
     
         14 . A compound for use, a method, or a use as claimed in  claim 12  wherein the virus is selected from the phylum Negarnaviricota, for example wherein the virus is selected from the order Monoegavirales, more specifically wherein the virus is selected from the family Paramyxoviridae, such as wherein the virus is selected from the genus Orthopneumovirus, such as wherein the infection is caused by a respiratory syncytial virus (RSV). 
     
     
         15 . A compound for use, a method, or a use as claimed in  claim 4 , wherein the parasite causing the parasitic infection is a unicellular protozoan parasite. 
     
     
         16 . A compound for use, a method, or a use as claimed in  claim 15  wherein the parasite is from the genus  Plasmodium , such as wherein the parasite is  Plasmodium Falciparum.    
     
     
         17 . A compound for use, a method, or a use as claimed in any of one of the preceding claims, wherein the treatment includes treatment of an infection in a patient caused by the microbe, such as the treatment includes treatment of an infection in a patient caused by the bacteria, parasite, fungus or virus. 
     
     
         18 . A compound for use, a method, or a use as claimed in  claim 17 , wherein the symptoms of the infected patient include one of the symptoms selected from the list consisting of fever, aching muscles, headache, cough, fatigues, nausea, pain, tiredness, vomiting, diarrhoea, nasal congestion, a sore throat, shortness of breath, increased mucus production, weight loss and a rash. 
     
     
         19 . A compound for use, a method, or a use as claimed in  claims 17  and  18 , wherein the treatment reduces or inhibits replication of the microbe, such as the parasite, bacteria, fungus and/or virus, in a patient, prevents infection of a patient by the microbe, such as the parasite, bacteria, fungus and/or virus, kills the microbe, such as the parasite, bacteria, fungus and/or virus in a patient and/or affects the immune system of a patient positively.